OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with obesity, and is now the most common liver disease in the United States. Cytokeratin 18 (CK18) is an intracellular protein released into the blood by both necrosis and apoptosis of hepatocytes. Levels of CK18 have not been reported previously in children with NAFLD. METHODS: In a cross-sectional analysis of 62 children (28 normal weight, 14 obese, and 20 suspected NAFLD), we measured CK18 levels as well as alanine aminotransferase, fasting glucose, fasting insulin, and tumor necrosis factor-alpha. RESULTS: CK18 was significantly elevated in the children with suspected NAFLD compared with obese controls and normal weight controls (median = 424 U/L compared with 243 and 214 respectively, P < 0.001). In multiple logistic regression analysis, CK18 was the best single predictor of suspected NAFLD (prediction accuracy = 84.1%). CONCLUSIONS: CK18 is elevated in children with suspected NAFLD and should be investigated as a potential diagnostic marker of NAFLD.